B cell receptor crosstalk: B cells express osteopontin through the combined action of the alternate and classical BCR signaling pathways.
Classical BCR signaling requires a number of signalosome mediators that are bypassed when BCR signaling follows an alternate pathway produced by prior exposure of B cells to IL-4. The two pathways, classical and alternate, co-exist in IL-4-treated B cells. Here we report that operation of the IL-4-induced alternate pathway in combination with the classical pathway changes the nature of the B cell response to BCR engagement so that the cytokine, osteopontin (Opn), is produced and secreted. Although Opn expression by B cells has not previously been noted, anti-Ig-induced secretion by IL-4-treated B cells amounts to levels comparable to those secreted by activated T cells. However, unlike T cell Opn expression, B cell expression of Opn is not mediated by T-Bet. Because elevated levels of IL-4 occur in association with severe illness, and because Opn is strongly associated with autoimmunity, these results suggest that the IL-4-induced alternate BCR signaling pathway may participate in the pathophysiology of autoimmune dyscrasias.
Guo
Benchang
B
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
Tumang
Joseph R
JR
Rothstein
Thomas L
TL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D053495:Osteopontin / Q000276:immunology / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000276:immunology / Q000378:metabolism*; D000098815:T-bet Transcription Factor
D011947:Receptors, Antigen, B-Cell; C506896:Spp1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D053495:Osteopontin; D015847:Interleukin-4